JPS62258368A - Production of quinazolin-4-one - Google Patents
Production of quinazolin-4-oneInfo
- Publication number
- JPS62258368A JPS62258368A JP5207186A JP5207186A JPS62258368A JP S62258368 A JPS62258368 A JP S62258368A JP 5207186 A JP5207186 A JP 5207186A JP 5207186 A JP5207186 A JP 5207186A JP S62258368 A JPS62258368 A JP S62258368A
- Authority
- JP
- Japan
- Prior art keywords
- quinazolin
- group
- formula
- alcohol
- anthranilic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 claims abstract description 30
- 150000002825 nitriles Chemical class 0.000 claims abstract description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims abstract description 3
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 3
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 5
- 229940102398 methyl anthranilate Drugs 0.000 abstract description 4
- ATMCEAIRSPRVAW-UHFFFAOYSA-N 2-tert-butyl-1h-quinazolin-4-one Chemical compound C1=CC=C2NC(C(C)(C)C)=NC(=O)C2=C1 ATMCEAIRSPRVAW-UHFFFAOYSA-N 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 238000007086 side reaction Methods 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 150000001408 amides Chemical class 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 150000002148 esters Chemical class 0.000 abstract description 2
- JAMNHZBIQDNHMM-UHFFFAOYSA-N pivalonitrile Chemical compound CC(C)(C)C#N JAMNHZBIQDNHMM-UHFFFAOYSA-N 0.000 abstract description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 25
- 238000000034 method Methods 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- -1 N-substituted amide group Chemical group 0.000 description 5
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- QYVWMIMELRGQGM-UHFFFAOYSA-N 2-pyridin-4-yl-1H-quinazolin-4-one Chemical compound N1C2=CC=CC=C2C(=O)N=C1C1=CC=NC=C1 QYVWMIMELRGQGM-UHFFFAOYSA-N 0.000 description 2
- WJXSWCUQABXPFS-UHFFFAOYSA-N 3-hydroxyanthranilic acid Chemical compound NC1=C(O)C=CC=C1C(O)=O WJXSWCUQABXPFS-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000008431 aliphatic amides Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 2
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- CHGWPLSMDGRLPO-UHFFFAOYSA-N 2-(furan-2-yl)-1h-quinazolin-4-one Chemical compound N1C2=CC=CC=C2C(=O)N=C1C1=CC=CO1 CHGWPLSMDGRLPO-UHFFFAOYSA-N 0.000 description 1
- SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- YXDXXGXWFJCXEB-UHFFFAOYSA-N 2-furonitrile Chemical compound N#CC1=CC=CO1 YXDXXGXWFJCXEB-UHFFFAOYSA-N 0.000 description 1
- NWPNXBQSRGKSJB-UHFFFAOYSA-N 2-methylbenzonitrile Chemical compound CC1=CC=CC=C1C#N NWPNXBQSRGKSJB-UHFFFAOYSA-N 0.000 description 1
- ZOQDGMRYMRFKRV-UHFFFAOYSA-N 3-methyl-2,1-benzoxazole Chemical compound C1=CC=CC2=C(C)ON=C21 ZOQDGMRYMRFKRV-UHFFFAOYSA-N 0.000 description 1
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は医薬、農薬、螢光剤などに有用なキナゾリン−
４−オンを、安価な原料を用い、反応試薬などを使用す
ることなく、より低い反応温度で、−反応工程により収
率よく製造する方法に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention provides quinazoline, which is useful for medicines, agricultural chemicals, fluorescent agents, etc.
The present invention relates to a method for producing 4-one in high yield through a -reaction process using inexpensive raw materials, without using reaction reagents, and at lower reaction temperatures.
従来、キナゾリン−４−オンを得るための方法としては
、アントラニル酸と脂肪族アミドまたはニトリルとの反
応が知られている。しかし、この反応は低級脂肪族アミ
ドまたはニトリル以外のものについては、目的物が得ら
れなかったり、収率がわるいという欠点を有していた。Conventionally, a reaction between anthranilic acid and an aliphatic amide or a nitrile is known as a method for obtaining quinazolin-4-one. However, this reaction has the disadvantage that the target product cannot be obtained or the yield is poor for substances other than lower aliphatic amides or nitriles.
そこで、この改良法として、ニトリルを出発物質とし、
イミダ−トあるいはＮ−ア′リール置換アミジンを合成
し、これらとアントラニル酸誘導体との反応による合成
法などが提案されている。また、これまで述べて来た反
応は、いずれも２００℃以上の反応温度を必要とし、熱
的に不安定な化合物の合成には不利であるという欠点を
有していた。Therefore, as an improved method, using nitrile as a starting material,
A synthetic method has been proposed in which imidate or N-aryl-substituted amidines are synthesized and these are reacted with anthranilic acid derivatives. Furthermore, all of the reactions described so far have had the disadvantage of requiring a reaction temperature of 200° C. or higher, which is disadvantageous for the synthesis of thermally unstable compounds.
本発明者はキナゾリン−４−オンの工業的製造法につい
て種々研究を重ねた結果、ニトリルとアントラニル酸ま
たはそのエステル、アミド誘導体とをアルコールの存在
下に加圧反応させることにより従来よりも低い反応温度
において、一段階の反応によりキナゾリン−４−オンが
収率良く得られ、しかも原料ニトリルについても、立体
障害を有するものも含めた広い範囲のものが使用できる
ことを見出し、本発明を完成するに到った。As a result of various studies on the industrial production method of quinazolin-4-one, the present inventor has found that the reaction rate is lower than that of conventional methods by subjecting nitrile and anthranilic acid or its ester or amide derivative to a pressure reaction in the presence of alcohol. The present inventors have discovered that quinazolin-4-one can be obtained in good yield through a one-step reaction at various temperatures, and that a wide range of starting nitriles, including those with steric hindrance, can be used, and in order to complete the present invention. It has arrived.
すなわち、本発明方法は、
一般式Ｒ１ＣＮ
（式中Ｒ１はアルキル基、アリール基、アラルキル基ま
たは複素環式基であって、これらはさらに置換基を有し
てもよい。）で表わされるニトリル（式中Ｒ２はＲ１と
同じ意味を持つか、または、水素原子、ハロゲン、ニト
ロ基またはヒドロキシル基であり、Ｒ３はヒドロキシル
基、アルコキシ基またはアミン基である。）で表わされ
るアントラニル酸またはその誘導体とをアルコールの存
在下に加圧反応させることを特徴とする
（式中Ｒ，、Ｒ２は前記と同様である。）で表わされる
キナゾリン−４−オンの裏造方法を提供するものである
。That is, the method of the present invention provides a nitrile ( In the formula, R2 has the same meaning as R1, or is a hydrogen atom, halogen, nitro group, or hydroxyl group, and R3 is a hydroxyl group, an alkoxy group, or an amine group. The present invention provides a method for producing quinazolin-4-one represented by the formula (wherein R, and R2 are the same as described above), which is characterized by carrying out a pressure reaction in the presence of alcohol.
本発明において用いる二゛トリルは次の一般式で表わさ
れる。Nitrile used in the present invention is represented by the following general formula.
Ｒ，ＣＮ （１）の置換基Ｒ１
は、ノ・ロゲン、ニトロ基、アルコキシ基、Ｎ置換アミ
７基などの反応に不活性な置換基をさらに有していても
よい。R, CN (1) substituent R1
may further have a substituent inert to the reaction, such as nitrogen, nitro, alkoxy, or N-substituted amide group.
本発明で用いるアントラニル酸マ゛たはその誘導体は次
の一般式で表わされる。Anthranilic acid or its derivative used in the present invention is represented by the following general formula.
式中Ｒ２は水素原子、ノ１０ゲン、ニトロ基、ヒドロキ
シル基、アルコキシ基またはＮ置換アミン基であるか、
あるいは、前記Ｒ１と同様な種々のアルキル基、アラル
キル基、アリール基または複素環式基であり、Ｒ３はア
ントラニル酸の場合ヒドロキシル基、アントラニル酸エ
ステルの場合アルコキシ基、アントラニルアミドの場合
はアミノ基である。In the formula, R2 is a hydrogen atom, a hydrogen atom, a nitro group, a hydroxyl group, an alkoxy group, or an N-substituted amine group,
Alternatively, it is the same various alkyl group, aralkyl group, aryl group, or heterocyclic group as R1 above, and R3 is a hydroxyl group in the case of anthranilic acid, an alkoxy group in the case of anthranilic acid ester, and an amino group in the case of anthranilamide. be.
本発明の方法は、前記したニトリルと、アントラニル酸
またはその誘導体とを、アルコールの存在下に加圧反応
させることにより、前記原料に対応する次の一般式で表
わされるキナゾリン−４−オンを良い収率で得るもので
ある。The method of the present invention produces quinazolin-4-one represented by the following general formula corresponding to the raw material by reacting the nitrile described above with anthranilic acid or its derivative under pressure in the presence of alcohol. It is obtained in terms of yield.
♂
（式中１（、、Ｒ２は前記と同じ意味を持つ。）本反応
において反応を速やかに進行させるためには、アルコー
ルの存在が必要であるが、その理由は、本発明における
反応が、式（４）に示すように、加圧下においてニトリ
ルとアルコールから生成するイミダートが、さらに式（
５）に示すようにアントラニル酸またはその誘導体と反
応し、キナゾリン−４−オンが生成するためと考えら扛
る。♂ (In the formula, 1 (,, R2 has the same meaning as above) In order to make the reaction proceed rapidly in this reaction, the presence of alcohol is necessary. The reason for this is that the reaction in the present invention is As shown in formula (4), the imidate produced from nitrile and alcohol under pressure further forms the formula (
This is thought to be due to the reaction with anthranilic acid or its derivatives to produce quinazolin-4-one as shown in 5).
（Ｒ３＝ＯＨ１ＯＲ，ＮＨ２）
本発明において使用するアルコール、！：してｔｄ、メ
タノール、エタノール、プロノくノールなどの低級アル
コールが用いられ、特にメタノールの使用が望ましい。(R3=OH1OR, NH2) Alcohol used in the present invention! : Lower alcohols such as td, methanol, ethanol, and pronocentol are used, and methanol is particularly preferred.
本発明においてアントラニル酸を使用する場合には、反
応速度を促進するために、塩基性溶媒の添加が望ましい
。適当な溶媒としては、アンモニア、またはメチルアミ
ン、エチルアミン、アニリンのような第１級アミン、ま
たは、ジエチルアミン、ピペリジンのような第２級アミ
ン、または、トリエチルアミン、ピリジンのような第３
級アミンが挙げられる。When using anthranilic acid in the present invention, it is desirable to add a basic solvent to accelerate the reaction rate. Suitable solvents include ammonia, or primary amines such as methylamine, ethylamine, aniline, or secondary amines such as diethylamine, piperidine, or tertiary amines such as triethylamine, pyridine.
and class amines.
本発明におけるニトリルとアントラニル酸またはその誘
導体との使用割合は、化学量論的には等モルであるが、
通常はモル比１：５〜５：１の範囲で選択される。また
、アルコールは、ニトリル１モルあたり０，１〜１０モ
ルの割合で使用される。The ratio of nitrile and anthranilic acid or its derivative used in the present invention is stoichiometrically equimolar;
Usually, the molar ratio is selected within the range of 1:5 to 5:1. Moreover, the alcohol is used in a ratio of 0.1 to 10 mol per mol of nitrile.
また、原料にアントラニル酸を使用する場合に添加する
塩基性溶媒の混合比もこれに準する。Furthermore, the mixing ratio of the basic solvent added when anthranilic acid is used as a raw material also conforms to this.
本発明を実施する場合、原料が相互に混合しにくいもの
である時は、適当な溶媒、たとえば、ジメチルアセトア
ミドなどに溶解して反応を行うことが可能である。When carrying out the present invention, when the raw materials are difficult to mix with each other, the reaction can be carried out by dissolving them in a suitable solvent such as dimethylacetamide.
本発明の反応は加圧下で行なわれ、高圧はど好ましいが
、一般的には１０００〜９０００ ａｔｍの間で選択さ
れる。反応温度は特に制約されないが、熱分解などの好
ましくない副反応をさける意味では、２０〜１５０℃の
温度の採用が望ましい。The reaction of the present invention is carried out under pressure, and although high pressure is preferred, it is generally selected between 1000 and 9000 atm. The reaction temperature is not particularly limited, but in order to avoid undesirable side reactions such as thermal decomposition, it is desirable to use a temperature of 20 to 150°C.
反応時間は圧力、温度等に作用されるが通常１〜５０時
間で十分である。The reaction time depends on pressure, temperature, etc., but usually 1 to 50 hours is sufficient.
本発明で得られる好ましい生成物を例示すると、立体障
害を有し、従来法では製造が困難であった２−（ｔ−ブ
チル）−キナゾリン−４−オン、２−（２−置換フェニ
ル）−キナゾリン−４−オンなどや、生理活性を有する
ものが多いところの複素環式基を有する２−（２−フリ
ル）−キナゾリン−４−オン、２−（２−チアゾリル）
−キナゾリン−４−オン、２−（４−ピリジル）−キナ
ゾリン−４−オンなどが挙げられる。Examples of preferred products obtained by the present invention include 2-(t-butyl)-quinazolin-4-one, 2-(2-substituted phenyl)- Quinazolin-4-one, etc., and 2-(2-furyl)-quinazolin-4-one and 2-(2-thiazolyl), which have a heterocyclic group and many have physiological activity.
-quinazolin-4-one, 2-(4-pyridyl)-quinazolin-4-one, and the like.
本発明は前記したように、キナゾリン−４−オン環を基
本骨格とする補々の化合物の要造法に適用するものであ
り、しかも、この場合従来法と比較して、合成できるキ
ナゾリン−４−オンの範囲が広く、また、反応温度が従
来法よりも非常に低いため、副反応などの進行を抑制す
ることができるうえ、反応工程が１段階であるため非常
に有利である。As described above, the present invention is applied to a method for producing complementary compounds having a quinazolin-4-one ring as a basic skeleton. Since the -on range is wide and the reaction temperature is much lower than in conventional methods, the progress of side reactions can be suppressed, and the reaction process is one step, which is very advantageous.
次に実施例によって本発明をさらに詳細に説明する。各
実施例中に示す部は重量部を表わし、また、収率に関す
るチは前記反応式（４）（５）におけるアントラニル酸
またはその誘導体についての理論収率である。Next, the present invention will be explained in more detail with reference to Examples. Parts shown in each example represent parts by weight, and q regarding yield is the theoretical yield of anthranilic acid or its derivative in the reaction formulas (4) and (5).
実施例１
アントラニル酸メチル１部、トリメチルアセトニトリル
（ビパロニトリル）１．０９部及びメタノール１．２５
部（モル比１：２：５．９）をテフロン裂カプセル中に
封入し高圧反応管中に収納して、約７０００ ａｔｍに
加圧した後、反応管を外熱して内部温度ｔ−１４０℃に
昇温し、さらに圧力を加えてｓ ｏ ｏ ｏ ａｔｍと
し、２０時間保持した。２０時間経過後反応管を室温ま
で冷却したうえで圧力を常圧とし、カプセルを取り出し
開封した。内容物をメタノールで洗い出し、減圧蒸留で
８０℃／ ２ ｍ ｒｒｌ−１９以下の沸点のものを除
き、残留物をイソプロピルエーテルまたはエチルエーテ
ルを用いて再結晶した結果、目的とする２−（ｔ−ブチ
ル）−キナゾリン−４−オン１．１５部（収率８６チ）
を得た。Example 1 1 part of methyl anthranilate, 1.09 parts of trimethylacetonitrile (biparonitrile) and 1.25 parts of methanol
(molar ratio 1:2:5.9) was encapsulated in a Teflon capsule and placed in a high-pressure reaction tube, pressurized to about 7000 atm, and the reaction tube was externally heated to an internal temperature of t-140°C. The temperature was raised to , and pressure was further applied to bring it to SOOO ATM, and the temperature was maintained for 20 hours. After 20 hours had passed, the reaction tube was cooled to room temperature, the pressure was brought to normal pressure, and the capsule was taken out and opened. The contents were washed out with methanol, and those with boiling points below 80°C/2 mrrl-19 were removed by vacuum distillation, and the residue was recrystallized using isopropyl ether or ethyl ether to obtain the desired 2-(t- butyl)-quinazolin-4-one 1.15 parts (yield 86 parts)
I got it.
実施例２
アントラニルアミド１部、２−トルニトリル１．７３部
及びメタノール１．４２部（モル比１：２：６）を実施
例１と同様に分別した結果２−（２−）リル）−キナゾ
リン−４−オン０．８２部（収率４７％）を得た。Example 2 1 part of anthranilamide, 1.73 parts of 2-tolunitrile and 1.42 parts of methanol (molar ratio 1:2:6) were fractionated in the same manner as in Example 1, resulting in 2-(2-)lyl)-quinazoline. 0.82 parts of -4-one (yield 47%) was obtained.
実施列３
アントラニル酸１ 部、’２ ） ’ジニトリル１．
フ０部、メタノール１．１６部、トリエチルアミン１．
４７部（モル比１：２：６：２）を実施イ刊１と同様の
手順で反応させ、同様に分別した結果、２−（２−１リ
ル）−キナゾリン−４−オン１．０３部（収率６０チ）
を得た。Example row 3 1 part anthranilic acid, '2)' dinitrile 1.
0 parts of fluorine, 1.16 parts of methanol, 1.1 parts of triethylamine.
47 parts (molar ratio 1:2:6:2) were reacted in the same manner as in Example 1, and fractionated in the same manner, resulting in 1.03 parts of 2-(2-1lyl)-quinazolin-4-one. (Yield: 60 cm)
I got it.
実施例４
アントラニル酸メチル１部２−フロニトリル０．６１部
及びメタノール０．６３部（モル比１：１：３）全実施
例１と同じ手順でｓ ｏ ｏ ｏ ａｔｍ、１００ ’
Ｃに２０時間保持した後、同様に分別した結果、２ °
１−（２−フリル）−キナゾリン−４−オン０．９８部
（収率７０チ）を得た。Example 4 1 part of methyl anthranilate 0.61 parts of 2-furonitrile and 0.63 parts of methanol (molar ratio 1:1:3) All in the same procedure as in Example 1, s o o o atm, 100'
After being kept at C for 20 hours, the same fractionation resulted in 2°
0.98 parts (yield: 70 parts) of 1-(2-furyl)-quinazolin-4-one was obtained.
実施例５
アントラニル俄メチル１部、４−ピリジンカルボニトリ
ル０．７８部及びメタノールＱ、９０部（モル比１ ：
１ ： ３．８０）を実施例１と同様の手順で６６０
Ｑ ａｔｍ 、 １００℃に２０時間保持した後同
様に分別した結果、２−（４−ピリジル）−キナゾリン
−４−オン０．９９部収率６９％）を得た。Example 5 1 part of methyl anthranil, 0.78 part of 4-pyridinecarbonitrile and 90 parts of methanol Q (molar ratio 1:
1:3.80) to 660 using the same procedure as in Example 1.
After holding the mixture at Q atm and 100° C. for 20 hours, it was similarly fractionated to obtain 0.99 parts of 2-(4-pyridyl)-quinazolin-4-one (yield: 69%).
実施例６
アントラニル酸メチル１部、２−チオフェンカルボニト
リル０．７２部及びメタノール０．６４部（モル比１：
１：３）を実施例１と同様の手順で反応させ、同様に分
別した結果、２−（２−チェニル）−キナゾリン−４−
オン０．５８４（収率３９チ）を得た。Example 6 1 part of methyl anthranilate, 0.72 part of 2-thiophenecarbonitrile and 0.64 part of methanol (molar ratio 1:
1:3) in the same manner as in Example 1 and fractionated in the same manner as in Example 1. As a result, 2-(2-chenyl)-quinazoline-4-
0.584 (yield: 39) of ion was obtained.
実施例７
３−ヒドロキシアントラニル酸１部、ベンゾニトリル１
．３４部、メタノール１．２５部及びアンモニア０．１
４部（モル比１：２：６：１．２）を実施グｊ１と同様
の手順で８０００ａｔｍ、１００℃に２０時間保持した
後同様の手順で分別した結果２−フェニル−８−ヒドロ
キシシナゾリン−４−オン１．３４部（収率８６％）を
得た。Example 7 1 part 3-hydroxyanthranilic acid, 1 part benzonitrile
．． 34 parts, methanol 1.25 parts and ammonia 0.1
4 parts (molar ratio 1:2:6:1.2) were held at 8000 atm and 100°C for 20 hours in the same manner as in Example J1, and then fractionated in the same manner, resulting in 2-phenyl-8-hydroxycinnazoline. 1.34 parts (yield: 86%) of -4-one was obtained.
Claims (1)
または複素環式基であり、これらはさらに置換基を有し
ていてもよい。）で表わされるニトリルと 一般式 ▲数式、化学式、表等があります▼ （式中Ｒ＿２はＲ＿１と同じであるか、または水素原子
、ハロゲン、ニトロ基、ヒドロキシル基であり、Ｒ＿３
はヒドロキシル基、アルコキシ基またはアミノ基である
。）で表わされるアントラニル酸またはその誘導体とを
アルコールの存在下に加圧反応させることを特徴とする 一般式 ▲数式、化学式、表等があります▼ （式中Ｒ＿１、Ｒ＿２は前記と同じ）で表わされるキナ
ゾリン−４−オンの製造方法。[Claims] A nitrile represented by the general formula R_1CN (wherein R_1 is an alkyl group, an aryl group, an aralkyl group, or a heterocyclic group, which may further have a substituent) and a general Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_2 is the same as R_1, or is a hydrogen atom, halogen, nitro group, hydroxyl group, and R_3
is a hydroxyl group, an alkoxy group or an amino group. ) with anthranilic acid or its derivatives under pressure in the presence of alcohol ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (wherein R_1 and R_2 are the same as above) A method for producing quinazolin-4-one.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5207186A JPS62258368A (en) | 1986-03-10 | 1986-03-10 | Production of quinazolin-4-one |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5207186A JPS62258368A (en) | 1986-03-10 | 1986-03-10 | Production of quinazolin-4-one |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62258368A true JPS62258368A (en) | 1987-11-10 |
Family
ID=12904585
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5207186A Expired - Lifetime JPS62258368A (en) | 1986-03-10 | 1986-03-10 | Production of quinazolin-4-one |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62258368A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0897915A1 (en) * | 1994-03-09 | 1999-02-24 | Newcastle University Ventures Limited | Quinazolinone conpounds as chemotherapeutic agents |
| WO2005117876A1 (en) * | 2004-06-01 | 2005-12-15 | University Of Virginia Patent Foundation | Dual small molecule inhibitors of cancer and angiogenesis |
-
1986
- 1986-03-10 JP JP5207186A patent/JPS62258368A/en not_active Expired - Lifetime
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0897915A1 (en) * | 1994-03-09 | 1999-02-24 | Newcastle University Ventures Limited | Quinazolinone conpounds as chemotherapeutic agents |
| WO2005117876A1 (en) * | 2004-06-01 | 2005-12-15 | University Of Virginia Patent Foundation | Dual small molecule inhibitors of cancer and angiogenesis |
| US8178545B2 (en) | 2004-06-01 | 2012-05-15 | University Of Virginia Patent Foundation | Dual small molecule inhibitors of cancer and angiogenesis |
| US8298512B2 (en) | 2004-06-01 | 2012-10-30 | University Of Virginia Patent Foundation | Methods of determining β-III tubulin expression |
| US8642610B2 (en) | 2004-06-01 | 2014-02-04 | University Of Virginia Patent Foundation | Dual small molecule inhibitors of cancer and angiogenesis |
| US9133136B2 (en) | 2004-06-01 | 2015-09-15 | University Of Virginia Patent Foundation | Dual small molecule inhibitors of cancer and angiogenesis |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2130924A1 (en) | Preparation of substituted guanidines | |
| JPH05507686A (en) | N-(2-biphenylyl)guanidine derivatives with therapeutic potential | |
| JP4389205B2 (en) | Preparation of 4-aminoquinazoline compounds | |
| EP0304941B1 (en) | Pharmaceutically useful polymorphic modification of buspirone | |
| JPS6212788B2 (en) | ||
| JPS62258368A (en) | Production of quinazolin-4-one | |
| AU618746B2 (en) | Process for polymorphic crystalline form conversion of buspirone hydrochloride | |
| US2621182A (en) | Office | |
| CA1126758A (en) | 1,1,3,5-substituted biuret compound and a pharmaceutical composition containing the same | |
| JPH05286936A (en) | Production of formamide derivative and new formamide derivative | |
| KR880001298B1 (en) | Method for preparing benzoyl-phenyl-piperidine derivatives | |
| US3061641A (en) | Anilinoalkyl-ureas | |
| Venkatesh et al. | Synthesis and anti-oxidant activity of some N-(anilinocarbonothioyl) benzamide and heterocyclic based thiourea derivatives | |
| JPS61186372A (en) | Production of benzothiazole | |
| JPH0236181A (en) | Asymmetric bisoxazolylpyridine derivative and production thereof | |
| JP2004511548A (en) | Method for preparing N-substituted 2-sulfanilimidazole | |
| HU206090B (en) | Process for producing new 1-phenyl-1,4-dihydro-3-amino-4-oxopyridazine derivatives and pharmaceutical compositions comprising such compounds as active ingredient | |
| JP3851368B2 (en) | Process for the preparation of substituted quinazoline-2,4-diones | |
| JP2690033B2 (en) | Method for producing 2,4-diaminoquinazolines | |
| JP5032732B2 (en) | Synthesis of chlorinated pyrimidines. | |
| Weis et al. | Dihydropyrimidines. 16. Stability and enamine-imine tautomerism in 1, 2-and 2, 5-dihydropyrimidines | |
| JP3067844B2 (en) | Method for producing N-alkylsulfonylaminosulfonylurea | |
| HU194193B (en) | Process for preparing new 4-/amino-methylidene/-3-aryl-5/4h/-isoxazolinone derivatives and pharmaceutical compositions containing such compounds as active ingredients | |
| JPS62198664A (en) | Production of pyridone-3-carboxamide | |
| Meena | Biologically active sulfonamides moiety: Synthesis, antimicrobial and antimalarial activity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |